Peptidyl aminosteroids as potential new antiarrhythmic agents.
The synthesis of peptidyl derivatives of the aminosteroid, amafalone (Am), is described. Six analogs were synthesized: the hydrochloride salts of Gly-Am (2) Ala-Gly-Am (3), D-Ala-Gly-Am (4), Pro-Am (6), Pro-Pro-Am (7), and D-Ala-Pro-Am (8). The peptide bonds were formed by the polymeric reagent method using polymeric hydroxybenzotriazole as the activating polymer. Peptidyl aminosteroids 2, 6, 7, and 8, when administered to rats intravenously, had protective antiarrhythmic effects similar to those of amafalone. By the oral route, less marked protection, in comparison to amafalone, was observed with 6, while 7 and 8 were disappointingly inactive.
Mokotoff
M
M
Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, PA 15261.
Zhao
M
M
Marshall
R J
RJ
Winslow
E
E
Wong
L K
LK
Liao
Q J
QJ
D000284:Administration, Oral; D000732:Androstanols / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis*; D007275:Injections, Intravenous; D013058:Mass Spectrometry; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology; D011355:Prodrugs / Q000138:chemical synthesis*; D051381:Rats
D000732:Androstanols; D000889:Anti-Arrhythmia Agents; D010455:Peptides; D011355:Prodrugs; C010158:amafolone